Monday, August 15, 2016

An accident of geography?



I was in the middle of a meeting. My cell phone rang. The number was unknown. I muted the phone. I called back after the meeting was done. It was an unknown male voice. He introduced himself as Abhijit Chatterjee*. He spoke in Hindi with a heavy Bengali accent. I found it difficult to follow what he was saying. But I could figure that he was talking about his daughter, Ananya Chatterjee* who was diagnosed with aHUS. She was currently on Peritoneal Dialysis.

I get roughly one call a month these days. After setting up the Atypical HUS India Foundation, putting up a website and a Facebook and Twitter account and trying to publicise the news that trickles in from time to time, people have been contacting me. My response is usually very standard. After all, nothing much changes in the grim, dark world of aHUS in India. No Eculizumab. No other good options for most of the mutations.

Over the next several weeks, I got introduced to Abhijit Chatterjee through a series of different people. The Atypical HUS Foundation in the US, aHUS UK, other aHUS family members from different parts of the globe. The man was desperately trying every source of information and help he could find on the internet. He contacted every person or organisation he found linked to aHUS. Unfortunately for Abhijit Chatterjee, all his efforts finally ended at my email Inbox or my phone.

My response was standard and offered little hope. “Eculizumab is the only good treatment for this disease. It is not available in India. Until it becomes available (this may take a few years more) or another drug becomes available, we need to do maintenance treatment like plasmapheresis, plasma infusions, dialysis etc.” I introduced him to some leading hospitals and clinicians so that he could talk to them first hand and see what other options might be available. He probably got similar answers from them as well.

On one call, Chatterjee talked about his daughter. I could sense the fondness he had for her, for little Ananya.

“She is so cute and innocent. She has no idea what is wrong with her. She has such a sweet face. I am feeling very helpless. I have spent lakhs of rupees on her treatment. I have borrowed money from everyone I know. I am not sure how I will repay them. I just want her to become well.”

As my eyes swelled, I could feel my gut wrench. What have we done to deserve this? Wouldn’t it have been better to have a disease that had no cure? It was so frustrating to know that there is a cure, there is a drug that can cure us completely. It’s just that we can’t afford it. It’s just that we were born in a country that did not have access to it.

Then, one day, there was suddenly a ray of hope. It came in the form of an email from a company that was working on a new complement inhibitor. They wanted to explore the possibility of conducting a clinical trial in India. As eculizumab was already available in countries like the US and the EU, it made perfect sense for them to do a trial in a country like India where there would be patients without any options and who might be perfect candidates for a trial.

I promised all help. Their Asia representatives were asked to contact me. I put them in touch with all the clinicians I knew who could have such patients. My hopes however came crashing down when I learnt that the company was currently enrolling only adult incident patients. That is adult patients who had just been diagnosed and had not proceeded to kidney failure.

I wrote to the company asking them to include paediatric patients as well as they would be able to enrol many more patients that way. The company responded that it would get back to me after discussing with the management. I haven’t heard back from them yet.

About a month back, I got a call from Abhijit Chatterjee again. They had sent Ananya’s blood samples for genetic testing. The reports showed a Complement Factor I Mutation. She would need Eculizumab for a transplant, I thought to myself. The doctors were recommending a kidney transplant. I asked him what the plan was in case of recurrence. He said he did not know. I asked him to discuss with the doctor that since they did not have eculizumab, what was the point in undergoing a kidney transplant especially if she had a Factor I mutation?

He said he would discuss with the doctor and get back to me. 

A couple of days back, Chatterjee called again. I thought he must be calling to update me about the transplant plan. However, I could immediately sense from his voice that this was something else. He sounded completely distraught. Little Ananya was admitted in the ICU at a very reputed hospital in South India. She had worsening blood counts. Her Platelet Count was dangerously low. She was put on a ventilator. They were monitoring very closely. I did not say much.

That evening I could not stop thinking about the little girl. 

The next afternoon, I got a call from Chatterjee. I was honestly scared to take the call. I feared the worst. I answered the phone after an excruciatingly long wait. Chatterjee broke down. “It’s all over. Last night, Ananya had a cardiac arrest, multiple organ failure and then she died.” I hung up. My heart sank. My throat choked. My mind went blank. Little Ananya was no more.

I muttered a curse to the skies. I asked myself what was wrong with this world? Of what good was all the progress mankind has made when the life of a little girl could not be saved merely due to an accident of geography? Why do people in some countries have access to the drug while others do not? 

Alexion Pharmaceuticals, the company that manufactures the drug has priced it so high that very few people in the world can afford it. Forbes magazine has declared their drug to be the most expensive drug in the world today. They have probably spent millions of dollars on the research for the drug. They have probably spent a lot of time, money and effort in navigating the various patent laws and making their drug available to people. Given that the number of patients in the world is so small, are they not justified in pricing their drug high enough to be able to make profits?

I honestly don’t know the answer to that question. All I know is that what happened to Ananya is just wrong. I don’t know what can be done to change the situation for aHUS patients in India and many other countries in the world where the drug is not available. Something needs to change. How many more such lives are going to be lost fighting this disease? How many more Ananyas are going to die before this situation is remedied? Someone needs to find a way out.

(* Names have been changed to protect identity.)

Friday, July 1, 2016

Updates from the aHUS UK and aHUS alliance meetings in London

I attended the aHUS UK patient meeting and the aHUS Alliance meeting in London during the last week of June. I learnt a lot of new things about aHUS. I am going to summarise the learnings here.

The biggest takeaway for me was that there are four new drugs in the pipeline to treat Atypical HUS. Dr. Wynne Weston-Davies of Volution Immuno Pharmaceuticals presented this information:

- ALN-CC5 from Alnylam
- Compstatin from Apellis
- OMS721 from Omeros
- Coversin from Volution

This should ideally result in a reduction of the price of Soliris from Alexion which would mean a better chance of access to it as well. Competition is always a good thing!

For more details on this, please click here

Each of these drugs acts in different ways but the end result would be similar - treatment of aHUS, at initial occurrence, subsequent occurrences, for kidney transplants etc. Another advantage of some of these drugs is that they could be administered by sub-cutaneous injection or even orally rather than the IV infusions that Soliris needs. There was also some talk about Alexion working on a sub-cutaneous version of Soliris.

All these drugs are still in early stages of development and clinical trials and may be years before they will be usable by patients in India. However, at least something is happening!

I also learnt of a new mutation that is implicated in aHUS - DGKE. This mutation unfortunately is not treatable by Soliris since it is not associated with complement activity.

Another important discussion that was had was the availability of complement inhibitors (currently only Soliris) in different countries. Here is a summary of the information:

Ideally, any patient should have access to a complement inhibitor (currently only Soliris) without having to pay out of pocket:

- At initial diagnosis
- Subsequent episodes
- During a Transplant and after to maintain the transplanted kidney

The following table summarises the situation in different countries with respect to this:

Country Status
France Full access
Italy Full access
UK Full access
Germany Full access
USA Full access
Russia Full access
Belgium Available for those with current aHUS activity, not available for transplants
Spain Available with some restrictions
Canada Available in some provinces and to others on a case by case basis
Netherlands Full access, future uncertain
Australia Available only for flairs and for a maximum of 12 months
India No access

*Full Access means access for all the above three situations

We had a good discussion on how to improve situations in countries where access is not complete.

Another discussion was had on the possibility of withdrawing Soliris and monitoring closely. This would reduce the cost per patient enabling more patients to get access to the drug. Patients were wary of this due to the risks involved.

Prof. Tim Goodship presented the history of aHUS treatment in the UK and said that currently a National Service has been created temporarily being managed by his team at Newcastle upon Tyne. The National Service is responsible to decide which patients should be given Soliris.

Overall, it was a great opportunity to meet so many others from different countries, each fighting the same battle. Here's a picture of the entire team:


Rare Disease Day 2015

Rare Disease Day is commemorated every year on the last day of February. From the Rare Disease Day website:

"The main objective of Rare Disease Day is to raise awareness amongst the general public and decision-makers about rare diseases and their impact on patients' lives."

What can you do on Rare Disease Day?

A lot!

For starters, you could change your Facebook and Twitter profile pictures to the Rare Disease Day logo which is available here. This will raise some questions among your friends and family about the day and you could explain.

You could also write a blog post on the topic.

There could also be a Rare Disease Day event in your city which you could participate in.

There is very little awareness about rare diseases in India. It is important for people to know about this. If people get to know, it would be that much easier to convince law-makers and people in important, influential positions to bring about change that would help patients afflicted by rare diseases.

Here is a link to the poster of this year's Rare Disease Day.

The Atypical HUS alliance website is live!

The website for the Global Alliance for Atypical HUS is up! Well, it is still under construction and has only the home page now but it will soon be completed with a lot more content. I am happy to let you know that Kamal from Atypical HUS India is a part of the group that is working on this website!

Check it out here.

Two case reports on aHUS after transplant

For those who have progressed to ESRD after aHUS, the possibility of a transplant is the most important question. Here is an article that reviews two cases of transplants in aHUS patients.

aHUS Global Alliance Meeting videos up on RareConnect

The aHUS Global Alliance had its meeting at Paris in November. As you might be aware, aHUS India also participated in the meeting via Videoconferencing. The videos of the meeting are now out and have been uploaded to Rare Connect, the umbrella organisation for all Rare Disease support groups from around the world.

You can access the videos here.

aHUS India's video is also up there!

International aHUS Awareness Day 2015

Yay! We finally have a Day!

Yes, the first ever International aHUS Awareness Day will be held on 24 September 2015. This will be a day to raise awareness about this disease, give a special shout for all those people affected by this disease. An extract from the announcement about this:

"The date is to be 24 September 2015, which was selected because it falls within the week that, 60 years ago next year , an article appeared in a clinical publication in Switzerland which contained the term Haemolytic Uraemic Syndrome for the first time. HUS was given its name by Conrad von Gasser,and his research team, to describe the illness they had been studying which caused blood clotting, anaemia and kidney failure, and which seemed to follow a gastric infection in some cases, or happened to several family members at different times in other cases."

Here is the link to the announcement from Len Woodward on rareconnect.

Long term outcomes data presented on efficacy of Soliris in aHUS

At the ASN's Kidney Week being held in Philadelphia, USA, researchers presented data from clinical trials of Soliris (Eculizumab) in patients with atypical hemolytic uremic syndrome (aHUS), as well as an update from the Global aHUS Registry.

Data was presented for a wide variety of patients including children and adults and both transplanted and non-transplanted patients.

This is very important because Soliris, being a new drug, not much is known about its long term implications. Such ongoing studies will really help to understand how it helps to maintain kidney function for long durations, an extremely important factor for aHUS patients.

More details can be found here.

India's patent laws - two sides of the debate


When I contacted Alexion Pharmaceuticals, the sole company in the world that manufactures Eculizumab, the only drug with which I can have a successful transplant, they said they had no plans to bring the drug to India. Their chief concern was India's weak IP protection laws.

In effect, they were worried that a local company could easily reverse engineer the drug and sell it at a fraction of the price. I was quite surprised that Indian laws would allow that. For a while, I assumed that they were referring to the illegal drug market where the drug would be copied in highly questionable conditions and sold illegally.

I was wrong. Indian patent laws allow reputed Indian manufacturers to reverse engineer drugs and sell them at a fraction of the price at which the original drug is sold by the company that actually invented the drug.

I read up a little on this recently. This issue was in the news after two significant rulings - on Novartis' Gleevec and Bayer's Nexavar, both cancer drugs. The rulings rejected the requests of these companies to prevent Indian companies from selling reverse engineered versions of the drugs at a fraction of the cost at which the originals were being sold.

There are a few things we must know. India used to provide only for process patents and not product patents. So, you could get a patent only for the way you produce a certain drug, not the drug itself. This changed in 2005, when due to India signing the WTO treaty required it to become TRIPS compliant which provided for product patents. However, some safeguards were provided which prevented MNCs from monopolising their products often to the detriment of the general public. It is often the interpretation of the safeguards that come up for litigation.

For example, there is a provision called Compulsory License where the country can allow a company to manufacture a generic version of a patented drug without the consent of the patent holder and sell it in the country by paying a certain royalty to the patent holder. Under what circumstances this can be done and what is the royalty that would be paid are all not specified clearly.

Look at all this from a big pharma company's point of view. They would believe that since they have the patent to the drug, no one must be allowed to sell it. In fact, the price at which Indian companies sell the drug is often a miniscule fraction of the manufacturer's price. Further, the cheaper version could also be exported to other countries and this could be disastrous for the patent holder! The pharma companies spend a lot of money on research and actually bringing the drug to the market. They believe that it is unfair to them to allow generic versions to be sold by someone else, at such low prices!

Fair point.

Now, look at this from a patient's point of view. There is a drug that is available in the market. The drug could save his life. But is priced so high that he cannot afford it. Or it is priced so high, his insurance / government will not pay for it. He would say this is completely unfair! He would argue that in the case of life saving drugs, commercial exploitation must not be allowed. When someone else is able to produce the drug and sell it much lower prices, this should definitely be allowed!

Again, fair point!

What is the way out?

A voice for Atypical HUS patients from India

My primary disease, Atypical Hemolytic Uremic Syndrome (aHUS) is classified as an ultra-rare disease. It affects about 1 or 2 in a million people.

Look at this from a doctor's perspective. A regular nephrologist would hardly see a handful of cases in his or her entire career! What is point in spending time in learning about this disease when there would be such little impact? The chances of anything new being learned to be actually put into practice would be almost zero! Why, then, must he or she not spend time on something that yields more 'bang for the buck'?

What about the pharmaceutical companies? When the total target population is a few hundred across the world, what incentive would be there for them to spend huge sums of money on research for drugs that could treat this disease? Its not like all the other possible work is exhausted and this is the only disease left, right?!

Where does this leave the Atypical HUS patient?

With little information forthcoming from doctors, not much advancement from pharmaceutical companies, we are left languishing, struggling to get back to 'normal'.

The situation is much worse in countries like India. While patients in some countries have access to Eculizumab, the one drug that could change their lives, India is not even on the radar for Alexion Pharmaceuticals to launch this drug in.

Why can't the drug be brought to India by patients who need them? It costs about Rs. 3.5 crore for a year's treatment and it could potentially be needed life-long. If there was a God, I would say, he has a sick sense of humour.

In all this gloom, it is important to find support. To reach out to people who are going through this hell just like you. That is why I started the Atypical HUS India Foundation. We have a website, a Facebook group and a Twitter account as well.

Chances are that you have nothing to do with aHUS. Chances are that the only place you've heard about this dirty disease is from me. But I would be really happy if you would take a minute, visit the website, like the FB page and follow the Twitter account (you can disable notifications if you like). The number of posts will anyway be very few. What worries me is when someone new is diagnosed with the disease, they would not find all this and that would rob them of a chance to get some support in dealing with this.

I plan to slowly add a forum and a latest news section in the website. I want to let Atypical HUS patients in India and their families know: You are not alone!

Thanks!